A new study from the Schizophrenia Research Laboratory highlights the importance of early detection of schizophrenia and further supports the idea that inflammation may be involved in the development of schizophrenia.

While there are strong indications that schizophrenia may have neurodevelopmental causes that occur before birth, there is an emerging idea that inflammation and neurodegeneration may be one of the reasons that a subset of people develops schizophrenia.

Our group of researchers in the Schizophrenia Research Laboratory at NeuRA have previously identified a subgroup of individuals with schizophrenia that displayed increased levels of inflammatory molecules in brain.

Dr Vibeke Catts recently delved deeper into this topic by investigating the link between schizophrenia and the presence of astrogliosis in post-mortem tissue. She found that the presence of reactive astrocytes in a subset of people with schizophrenia could be a result of inflammation occurring within the brain.

Astrocytes are cells that are found in the brain and spinal cord that are responsible for a host of structural, metabolic and repair activities. When there are an abnormally large number of reactive astrocytes present in the brain, known as astrogliosis, it may be due to the destruction of nearby neurons or an indication of inflammation in the brain.

“What this study highlights is that if schizophrenia is related to tissue damage, then we shouldn’t wait to intervene,” explains Dr Catts. “The earlier the intervention, the less opportunity for damage to be caused by the gliosis.”

It is hoped that, in the near future, we may be able to use peripheral inflammation markers in the blood to help determine the subset of people with schizophrenia who have elevated inflammation and thus introduce treatment options at the earliest stage to those who may benefit from this therapy.

“We know, as a result of studies into the cognitive aspect of schizophrenia, that some people experience deterioration in cognitive function and IQ while others remain stable. And it may be the case that the people whose cognitive functions deteriorate may have experienced a gliosis reaction. If that’s the case, the closer to onset that we can introduce an intervention, the more likely we are to help maintain the cognitive processes.”

“Research has shown that in diseases such Alzheimer’s it is ideal to identify the issue early, before too much damage has occurred, and it is the same with schizophrenia. From a clinical perspective, our results suggest that early intervention is ideal.”

Dr Dipesh Joshi has been exploring an exciting new target for the development of next generation antipsychotics that will improve more than just the positive symptoms of schizophrenia.

Dipesh Joshi, who is a member of the Schizophrenia Research Lab at NeuRA in Randwick, has been investigating how structural cellular changes in the brains of people with schizophrenia may be related to a specific gene that is associated with the risk of developing schizophrenia.

Neuregulin 1 and its receptor ERBB4 are both linked to schizophrenia susceptibility and are both involved in important neurobiological processes associated with some cognitive symptoms of schizophrenia. Dr Joshi is keen to find out how this gene and receptor combination are altered in the brains of people with schizophrenia as the answers may provide us with new target treatments for antipsychotic medication. Currently antipsychotics work mostly on the positive symptoms of schizophrenia and do little for the negative or cognitive symptoms.

“What we have achieved in this study is an exciting step forward,” says Dr Joshi. “We have linked genes that place people at risk of developing schizophrenia with a type of brain cell that maintains the inhibitory and excitatory balance in a normal brain. In schizophrenia, the inhibitory interneuron is reduced and we have linked this reduction to an alteration in ERBB4, which contributes to the development of schizophrenia.”

Figuring out how ERBB4 works in the brain will be the next challenge that, once it is achieved, will allow researchers to develop treatments, such as a new generation of antipsychotics, that will improve the functioning of the receptor.

A generous grant offered to our researchers by SunCorp has resulted in an exciting new co-treatment approach that could reduce the weight gain side effects of some antipsychotics.

A venomous lizard usually found in the wilds of Mexico and Arizona has given researchers fresh inspiration for a treatment that can counterbalance one of the main side effects of antipsychotics. The saliva of the Gila (pronounced hee-la) Monster contains a protein that has been found to reduce blood glucose levels. Second generation antipsychotics such as olanzapine and clozapine often cause the unwanted side effects of hyperglycaemia (high blood sugar) and Type II diabetes, however it has been found that the lizard’s protein can help to control these issues.

Remarkably, this protein is very similar to a hormone already found in the human body that helps to regulate levels of insulin and glucagon (a hormone that increases the level of blood glucose). A synthetic replication of the Gila Monster’s protein, called liraglutide, has since been created and approved for therapeutic use as an anti-diabetic drug in the US, Europe and now Australia.

The efficacy of liraglutide in stabilising glucose levels and promoting weight loss caused our researchers, led by Dr Katrina Green, to investigate whether the drug could be used as a co-treatment with current antipsychotics such as olanzapine and clozapine. Results of an initial study, which was supported by funds raised via the SunCorp Brighter Futures program, have revealed that using liraglutide as a co-treatment alleviated olanzapine-induced glucose dysfunction, but not the hyperglycaemia caused by clozapine.

“This tells us that liraglutide is effective at clearing glucose from the blood,” explains Dr Green, “which may prevent diabetes, a common side effect associated with olanzapine, in the long term. We still need further studies to investigate other potential metabolic benefits of liraglutide co-treatment, such as weight loss and cardiovascular protection, however the results are looking very promising so far.”

Diabetes has also been shown to exacerbate cognitive deficits in people with schizophrenia, so there is hope that using liraglutide as an adjunct treatment can also improve impairments in attention and memory. “This is something we really want to focus our future studies on,” says Dr Green. “We’re keen to start looking into the potential long term cognitive effects that liraglutide may bring.”

There have been several papers published in peer-reviewed journals over the past few months, some of which we have highlighted here to share with you the progress our scientists are making when it comes to understanding how we can better treat schizophrenia.

Dr Kelly Newell (pictured) believes that drugs that target the mGluR5 receptor in the brain may be useful in the treatment of schizophrenia, but there still remain several research questions that need to be explored before proceeding with clinical trials. Dr Newell, together with SRI PhD candidate Natalie Matosin, has recently published an opinion piece outlining these areas in the hopes that relevant pharmaceutical companies will make use of the research.

“Pharmaceuticals are in the process of developing and getting drugs to clinical trials and we’re supporting that by making sure that they move forward with the right research,” she explains. “These drugs could be useful not just for schizophrenia but for treating depression as well, which forms part of the argument that more research needs to be done. This paper will hopefully go towards influencing the design and implementation of potential therapeutic drugs.”

Research such as this has a great impact on clinical trials. “When you get the underlying science right, you’re more likely to succeed,” says Dr Newell, “so we’re reminding them of areas of research that haven’t yet been considered. We’ve raised a number of points that may help to avoid problems in future clinical trials.”

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Dr Ans Vercammen has published a paper that outlines how researchers now understand more about the interplay between genes and how that affects schizophrenia, specifically its cognitive-affective challenges. Working as part of the Schizophrenia Research Laboratory*, Ans has found a number of indicators that point to the presence of dopamine-related genes in healthy people that, when combined, produce brain responses similar to schizophrenia. “Knowing this will help us to better understand how genes link to particular symptoms of schizophrenia, and may help us to tailor treatments in the future,” she says.

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Dr Grant Sara has developed improved methods for extracting information from large health databases to help scientists to identify information that will assist them in their research. Some of the big questions in schizophrenia research can best be answered when scientists take a bird’s eye view of a whole population.

“Research based on large datasets can provide important information that helps to complement clinical research,” explains Dr Sara. “The bird’s eye, or epidemiological, perspective might help us to answer questions such as how people’s diagnoses evolve over time; whether some treatments or types of service are more effective than others; whether people are accessing the services they need; how drugs such as cannabis and stimulants impact on people with psychosis; what are the patterns of physical illness and physical health care for people with a diagnosis of schizophrenia, etc. Research on any of these questions has to start with an accurate diagnosis.”

Dr Sara used diagnostic information from people who had been interviewed by researchers as part of a national survey of people with psychosis and who gave permission for this information to be linked to state health databases. He tested a range of possible methods to find the most accurate method for defining a diagnosis of schizophrenia or bipolar disorder.

The algorithm he devised should help future researchers by making it quicker and more accurate to extract diagnostic information for research studies, which will help researchers to answer some of these important questions.

* The Schizophrenia Research Laboratory is a joint initiative of the Schizophrenia Research Institute, University of New South Wales, Neuroscience Research Australia (NeuRA) and the Macquarie Group Foundation. It is supported by the NSW Ministry of Health.

Cognitive Behavioural Relating Therapy tips the balance of power in favour of people with schizophrenia and allows them to develop a healthier interpersonal relationship with the voices they hear.

Cognitive Behavioural Relating Therapy (CBRT) is a novel treatment developed by Perth-based psychologist Dr Georgie Paulik that aims to improve how people relate to the voices they hear, as well as other people socially, and decrease the amount of distress caused by persistent voice-hearing.

This Institute-supported researcher and therapist found, through her experience in clinical practice, that many voice hearers perceived the voices to have greater power and assertiveness relative to themselves, which caused distress and made many feel reluctant to develop a relationship with the voices.

Dr Paulik discovered that teaching people how to relate to these voices with a sense of authority and intimacy was an effective way to overcome this obstacle. “Some people didn’t want to engage with their voices, as there was an element of fear and intimidation in the relationship, so teaching them how to respond assertively helped to improve this relationship,” Dr Paulik explains. “CBRT encourages people to question the beliefs they hold about a voice’s power and the way in which they relate to the voices, which improves the relationship between the voice and voice hearer and, subsequently, can improve how they relate socially to other people too.”

The therapy was initially developed to be used in one-on-one sessions but has since grown to include group therapy sessions. Study results investigating the efficacy of CBRT have found that participants expressed positive changes in the way they related to the voices, improved-self esteem and reductions in voice-related distress.

“Everyone involved has been really positive, there have been no dropouts,” says Dr Paulik. If you are interested in pursuing CBRT with your therapist, contact the Institute (contact@schizophreniaresearch.org.au) and we’ll pass your details on to Dr Paulik who can share the workbooks and materials with your therapist.

An 18-month labour of love has resulted in a paper that brings together current information on schizophrenia research and where to go from here.

Sandra Matheson (pictured) set herself a herculean task in order to contribute to the research field’s understanding of schizophrenia by reading and assessing the latest systematic review papers from various current avenues of research. “Researchers can sometimes get focused on their own particular areas of interest,” she says. “My hope is that this paper will help people to think outside the square. When someone in neuroscience, for instance, reads about the latest findings in epidemiological studies it may help them to cross boundaries and join dots they wouldn’t otherwise have thought about.”

In creating this overview of schizophrenia research, Sandy concluded that while our knowledge of schizophrenia is very substantial, a deep understanding of it remains limited.

The good news is that there were several key areas of research that were particularly noteworthy in terms of the strength of evidence and size of the effect. The efficacy of psychosocial treatments when used in concert with medication, particularly when administered in the early stages of psychosis, and studies exploring the involvement of infection and immunological markers on the development of schizophrenia, were two stand-outs.

Volunteers are invited to register their interest in a study that aims to investigate whether we can improve cognitive function (thinking ability) and reduce auditory hallucinations (hearing voices) with the use of a technique called Direct Current Stimulation (DCS). DCS delivers a very weak electrical current to particular brain regions via a small electrode pad placed on the scalp. This painless and non-invasive technique has been used successfully in many other applications including the treatment of depression. Recent findings suggest that it can also be beneficial in treating other symptoms.

Volunteer participants will receive a daily 20 minute session of DCS for 2-4 weeks (week days only). They will also take part in an assessment of their symptoms and cognition before the treatment and after the treatment. A brain scan is optional. Participants are reimbursed for their participation.

Kathleen Smith found a way to help manage one of her symptoms and can now share it with others.

While anxiety can be a common occurrence in schizophrenia, it doesn’t have to be a constant companion. For one of our patient ambassadors, Kathleen Smith, anxiety would rear its head on a daily basis until her psychologist taught her a mindfulness technique that allowed her to concentrate on her senses and be in the present moment. “The technique is all about letting go of things that are stressing me,” she says. “It’s about lightening my load.”

Kathleen, who is a graphic designer, created an app for her phone that featured a leaf floating down a stream so she could access it quickly and discretely at any time of the day. If she became anxious or overwhelmed, Kathleen would visualise placing the problem on the leaf then watch as it floated away from her until it was out of sight. When she showed the app to her psychologist and psychiatrist they were extremely impressed. “Both of them said that I should develop it a bit more and get it out there,” she explains. “So I created a few more images that would help with the visualisations then made it into an app that can be downloaded through Google Play. I’ve found it really helpful and others have too.”

The app costs 99 cents to download and Kathleen will donate 50 percent of the proceeds to the Institute. “It’s such a simple concept,” Kathleen says, “I really wanted to share it with other people who, like me, are looking for ways to manage their schizophrenia every day.”

Our Newcastle scientists have created a way to increase the opportunities for young people at risk of developing schizophrenia to access expert help sooner.

Professor Ulrich Schall, based at the University of Newcastle, initiated the Minds in Transition (MinT) study in order to better understand what may be occurring in the brains of young people who are at risk of developing a severe mental illness. Now, Prof. Schall and his team have won a grant from the Hunter Medical Research Institute that will allow them to translate their recent study findings into a clinical setting and assist youth to access the mental health services they need.

Along with substance abuse problems, emerging mental health problems are the most significant factors that affect the health of young people; however, most only receive the help they need once a severe, and often life-long, mental illness is established. “We’d like to combat this,” Prof Schall explains. “We know that the earlier a person is able to access treatment, the better their recovery outcomes are likely to be, so we’ve used the information we gathered during the MinT study, which looked at the early signs and symptoms that indicated a person was likely to transition into psychosis, and have developed a model of care that will allows GPs to identify which of their patients may be likely to do so.”

Once a doctor has established that a patient under their care may need further mental health assistance, the health care referral system developed by Prof. Schall and his team will ensure that young people have access to specialists that are experienced in assisting those with an emerging mental illness. “Until we can actually prevent people from having to suffer a mental illness, this is the next best thing we can currently do,” says Prof. Schall. “By ensuring that young people have easy access to professionals trained to reduce the impact of an illness such as schizophrenia, we are improving their chances to lead a much healthier life.”

Research Area: The changes in hippocampal neurogenesis in adolescent brains and the effect of testosterone on neurogenesis and neurotrophins (ie neuronal growth factors) expression in adolescence.

Educated: Bachelor of Medical Sciences (Hons) from Macquarie University

Doctorate: Currently working on PhD at UNSW supervised by Prof. Cyndi Shannon Weickert

Personal Interests: Cooking and dancing

Curiosity led Katie Allen to start her career in schizophrenia research, but the opportunity to bring about real change in people’s lives has encouraged her to continue her search to understand the causes of schizophrenia. A PhD student who graduated from Macquarie University, Katie has worked in the Schizophrenia Research Laboratory* for more than four years under the supervision of Dr Samantha Fung, Dr Tertia Purves-Tyson and Professor Cyndi Shannon Weickert.

Her area of interest lies in investigating the changes that occur in the adolescent brain, specifically the levels of testosterone and the effect they have on the hippocampus. “There have been lots of studies into adult brains but not a lot in adolescence and we’re particularly interested in this period of time because this is often when schizophrenia develops,” Katie explains.

The hippocampus is a small region of the brain that is involved with memory formation and learning as well as organising and storing information. It is also an area in which the process of neurogenesis occurs; that is, new neurons are created, which can result in improved function of the brain.

It is also known that men are more likely to be diagnosed with schizophrenia and that testosterone could be a trigger for the illness, which got Katie and others in her team to wondering what effect testosterone may have on neurogenesis and why it might be decreased in people with schizophrenia. “We’re trying to piece together what happens in the development of schizophrenia by focusing on this area of the brain,” Katie says. “If we can understand why certain people have a decrease in neurogenesis, we then have the opportunity to figure out how to prevent it and possibly even reverse it.”

The end goal for Katie is not only to fill in the blanks that currently exist in our knowledge of how schizophrenia develops, but to find out which aspects, such as testosterone levels, could be changed such that better treatments or a cure could be developed as a result. “I want to know why schizophrenia has its onset in late adolescence, it’s quite a mystery to me,” she admits. “Why not earlier? Puberty and adolescence are such important times in a person’s life, it would be good to know what is going on in the brain at those times.”

If you would like to support our scientists as they find ways to understand, better treat, prevent and cure schizophrenia, please consider donating. A regular gift of just $5 a month will help them to achieve their goals.

*The Schizophrenia Research Laboratory is a joint initiative of the Schizophrenia Research Institute, Nerouscience Research Australia (NeuRA), the University of New South Wales and Macquarie Group Foundation. It is supported by the NSW Ministry of Health.